Development of a Two-Step, Enantioselective Synthesis of an Amino Alcohol Drug Candidate
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- 作者：Michael A. Schmidt ; Emily A. Reiff ; Xinhua Qian ; Chao Hang ; Vu Chi Truc ; Kenneth J. Natalie ; Chenchi Wang ; Jacob Albrecht ; Andrew G. Lee ; Ehrlic T. Lo ; Zhiwei Guo ; Animesh Goswami ; Steven Goldberg ; Jaan Pesti ; Lucius T. Rossano
- 刊名：Organic Process Research & Development
- 出版年：2015
- 出版时间：September 18, 2015
- 年：2015
- 卷：19
- 期：9
- 页码：1317-1322
- 全文大小：283K
- ISSN：1520-586X
文摘
The process development and large scale synthesis for the 尾-hydroxyamino amide 1 is described. The route evolved from a multistep sequence utilizing a classical resolution to a two-step enantioselective process involving an enzyme-catalyzed aldol reaction and a direct amidation of a carboxylic acid. By utilizing a silicon-mediated direct amidation strategy, the route was devoid of protecting and deprotecting steps while retaining the stereochemical integrity of a highly sensitive 尾-hydroxyamino acid. The two-step strategy employed herein significantly improved the yield, process greenness, cycle time, and estimated cost in the production of 1.